Single photon emission computed tomography (SPECT) is a nuclear medicine procedure in which a rotating gamma camera is used to obtain cross- sectional images depicting anatomy and physiologic function. New developments in radiopharmaceuticals as well as imaging instrumentation have recently stimulated a renewed interest in brain imaging. One promising application of SPECT brain imaging is the localization of epileptogenic seizure foci which is used as a non-invasive ancillary method for pre-Operative evaluation of patients with refractory complex partial seizures. It is possible that SPECT imaging can obviate the need for the invasive and expensive intracerebral EEG procedure commonly used as a pre-operative step to accurately localize seizure foci. The goal of this proposal is to improve the diagnostic accuracy of seizure foci localization obtainable with SPECT imaging. This will be accomplished by the development of three novel reconstruction approaches which will minimize the degradations caused by scattered radiation, photon attenuation, non-stationary spatial resolution, and statistical noise. The first approach will involve processing the measured projection data with a separate compensation procedure for each degradation (ie., scatter, attenuation, and detector response blurring) and then reconstructing with filtered backprojection. The second and third approaches will use iterative Bayesian reconstruction. A major focus of this proposal will be to develop techniques to substantially reduce the computational load of iterative reconstruction. This will primarily be done by using the frequency distance principle as a computationally efficient means of modelling distance- and depth-dependent blurring. For comparison and testing of the methods, simulated and clinical acquisitions will be obtained. A mathematical, 3D anthropomorphic brain phantom, which has the capability of specifying source densities and attenuation properties of different neuroanatomical structures will be input into a Monte Carlo SPECT simulation program to create realistic projection sets. Patient studies with confirmed unilateral temporal lobe foci will also be used for analysis. To assess and compare the performance of each reconstruction approach, experiments will be performed to measure the quantitative and visual accuracy of seizure foci localization and lateralization.